Disease/Drug of interest:

Neisseria Meningitides/ Benzyl penicillin

Meningitis.jpg

Figure 1. A before and after picture displaying neisseria meningitides in the brain of a young child.

Motivation and Background:

What exactly is neisseria meningitides ? Meningitides is an illness that is an contagious infection, a disease that is common in about one tenth of adults. It is a disease that causes the Inflammation of the protective membrane covering the brain and the cerebral spinal fluid(1). The pia mater, which is closest to the central nervous system, the arkanoid in the dura mater which is furthest from the brain. These membranes are covered by a lot of blood vessels and cerebrospinal fluid.(1)
meninges_of_cns.jpg
Figure 2: Shows the layer of the brain that neisseria meningitides interacts with.
Specifically the dura mater, arachnoid, and the Pia mater.

The symptoms of bacterial meningitis can vary from things like headache, neck stiffness, more severe symptoms would be seizures or a coma. This bacterium is more common among infants however any age group is at risk. (7) To determine if someone has meningitis samples of blood or cerebrospinal fluid is collected and tested. If we are able to determine the specific interactions within the bacterial cells and the brain cells. This could possibly lead to a domino affect leading to many unresolved mysteries! For example,the study of meningitides could lead to the study of seizures. The interactions between cells could be inhibiting or causing some form of hyperpolarization or depolarization within the cell maybe even something affecting the proteins on synaptotagmin. Which is the key protein affecting the release of neurotransmitters there is so many unresolved mysteries within the brain I believe if we are able to start with the minute study of neisseria meningitides and its interactions we will come up with many untold secrets of the brain and will be able to determine the causes of seizures. This could help kids who are determined to be autistic. Autism is something Aditi Shankardass classifies as little seizures in the brain.


Facts about epilepsy
  • 1 in 26 of us citizens develop epilepsy in their lifetime
  • 3 million U.S citizens live with epilepsy
  • two-thirds of patients with epilepsy causes are unknown.
This is only one example of the impact that the study of neisseria mengitides could lead to.

External links:


Target Information:

The drug benzyl penicillin is the drug is used more commonly to treat the bacteria in its early stages. It works by binding to transpepetidases and preventing it from binding and inhibiting the crosslinking of the peptidoglycan subunits. The cell walls of bacteria are very important .It protects the DNA of the bacteria. Their genetic material is maintained in the nucleoid, which is their cytoplasm. There are 2 major components of the bacterial cell wall gram positive and gram negative. Gram positive bacteria has a thick cell wall and is made up of many layers of peptidoglycan and teichoic acids.(4) Peptidoglycan in bacteria cell walls increases their strength and keeps its contents not from leaking out, as well as other external substances from getting in. Peptidoglycan is composed of glycan polymers that are cross-linked bonded to one another by short peptide side chains. (4) It has two to five layers depending on its stage in growth. The peptidoglycan provides the structural framework of the cell wall, teichoic acids, which make up about 50% of the cell wall material, this is thought to control the overall surface charge of the wall. Both peptidoglycan and teichoic acids are polymerized on the surface of the cytoplasmic membrane, however they are assembled together in the cytoplasm.(4) Anything that interferes with the assembling of the molecules and its transport across the membrane to fuse with the cell wall, could significantly damage the cell wall. Damage to the cell wall disturbs the balance of cell electrolytes, which can activate death pathways. Which the cell will sacrifice cells for the benefit of the remaining cells. A gene-encoded program will activate PCD(program cell death). (5)The point about this activation is the apoptosis, which activates a family of cysteine aspartyl. The inactivated proenzymes work together in a controlled cascade to activate one another. These capiases cleave a number of structural proteins and enzymes by disassembling itself and its contents. In summary with a damaged cell wall the integrity of the bacterial DNA could be at risk. (4) Which is essential to the processes of binary fission. This means even if it doesn’t die from this could reduce or subside the rate of replication of the bacteria. This is a very effective method to killing the bacteria but as time progresses like any bacteria there are few reports of the bacteria having a resistance to the drug.

In turn this could influence the polarization of the cells within the brain which could cause insufficient firing of action potential within the cell. Action potentials are essential to day to day activities. Any disturbance in the brains natural balances could cause severe consequences.

Size: molecular weight of the protein


41,000-91,000

(MW 334.4G/Mol)



Location:

This protein is found through out the body in blood cells



Function in a normal cell:

meningococcas.jpg

Figure 3: Shows the structure of a bacterial cell consistent with neisseria meningitidis.The structure shows: the bacterial cell wall, the membrane, its organelles , and also the polysaccharide capsule in which is used to classify the different types of bacterial cells that comes with neisseria meningitidis

Drug Information:


Schematic figure of drug:
Untitled.png
Figure 4: shows the 2d structure of the drug Benzyl-penicillin
Formula:
C16H18N2O4S

Molecular weight:
MW 334.4G/Mol)

CAS Number:
CAS 61-33-6
Delivery method:
Is administered in a variety of ways. Injection (intravenous and intramuscular) and pill is the most common way.

Side effects:
Pain , Nausea, Vomiting, diarrhea, fever, seizure, and headache

Other names:
Ben Pen

Maker or company:
Corden Pharma
Is it patented?

US2532980 A

Dec 5,1950
Inventors : Harold B Woodruff, Alma H Larsen


Clinical Trials Info:

Origin:
The discovery of penicillin capabilities is credited to Alexander Fleming a professor of bacteriology at St. Mary’s hospital in London.(3) The Story goes that as Alexander Fleming returned from the holidays on September 3rd 1928 through a collection of petri-dishes containing staphylococcus (bacteria that produces boils and sore throats) he noticed on a dish that is was dotted with colonies that were growing in the dish, and in one area mold was growing.(3) This mold deemed “mold juice” later to be determined as a different strain of penicillin. This “mold juice” was later studied by other scientist and enhanced to treat a number of bacterial infections.
Alternatives to this drug:
Alternatives to Benzyl Penicillin include: vancomycin , Vancocin rifampin, gentamicin, ceftriaxone, Claforan. All different forms of antibiotics used to stop the growth of bacteria.

Other uses: can this drug be used to treat other diseases/conditions?
This drug can also be used to treat Cellulitis, aspirations, pneumonia, septic arthritis, gangrene, diphtheria

References:
  1. Lee, D.; Kim, E. J.; Kilgore, P. E.; Takahashi, H.; Ohnishi, M.; Tomono, J.; Miyamoto, S.; Omagari, D.; Kim, D. W.; Seki, M., A Novel Loop-Mediated Isothermal Amplification Assay for Serogroup Identification of Neisseria meningitidis in Cerebrospinal Fluid. Front Microbiol 2015, 6, 1548.
  2. Sheikhi, R.; Amin, M.; Hamidinia, M.; Assarehzadegan, M. A.; Rostami, S.; Mojtahedi, Z., Comparative Proteomics Analysis of Two Strains of Neisseria meningitidis Serogroup B and Neisseria lactamica. Jundishapur J Microbiol 2015, 8 (11), e25228.
  3. American Chemical Society,. Alexander Fleming Discovery and Development of Penicillin - Landmark http://www.acs.org/content/acs/en/education/whatischemistry/landmarks/flemingpenicillin.html (accessed Feb 11, 2016).
  4. The Cell Wall Of Bacteria. Boundless 2015.
  5. Lewis, K. Programmed Death In Bacteria. Microbiology and Molecular Biology Reviews 2000, 64, 503.
  6. Workshop,. Programmed Cell Death in Model Organisms http://events.embo.org/12-cell-death/ (accessed Feb 11, 2016).
  7. Prevention, C. Meningitis | About Bacterial Meningitis Infection | CDC http://www.cdc.gov/meningitis/bacterial.html (accessed Feb 11, 2016).
  8. Newman, T. Penicillin: How Does Penicillin Work? http://www.medicalnewstoday.com/articles/216798.php (accessed Feb 11, 2016).
  9. Prevention, C. Meningitis | Lab Manual | Epidemiology | CDC http://www.cdc.gov/meningitis/lab-manual/chpt02-epi.html (accessed Feb 11, 2016).
  10. Cdc.gov,. Meningococcal | Causes and Transmission | CDC http://www.cdc.gov/meningococcal/about/causes-transmission.html (accessed Feb 11, 2016).
  11. Prevention, C. Meningitis | Lab Manual | Epidemiology | CDC http://www.cdc.gov/meningitis/lab-manual/chpt02-epi.html#f18 (accessed Feb 11, 2016).
  12. Rahman, M. M.; Hunter, H. N.; Prova, S.; Verma, V.; Qamar, A.; Golemi-Kotra, D., The Staphylococcus aureus Methicillin Resistance Factor FmtA Is a d-Amino Esterase That Acts on Teichoic Acids. MBio 2016, 7 (1).
  13. Cure epilepsy, Web http://www.cureepilepsy.org/aboutepilepsy/facts.asp

Pictures
  1. 1. Dg743, Bacterial Meningitis and Neisseria Meningtidiis Web http://citesource.trincoll.edu/acs/website_002.pdf (accessed February 27, 2016)
  2. 2. Jwi.Healthy, Web http://jasawebinet.com/meningococcal-meningitis/ accessed (February 28, 2016)